Identification of health- and disease-associated bacteria for chronic otitis media with effusion through microbiome comparison and in vitro experimentation
9 oktober 2020
Online - - - - -
Organisatie / co-organisatie:
Sarah Lebeer & Olivier Vanderveken
UITGESTELD - Online Doctoraatsverdediging Jennifer Jörissen - Faculteit Wetenschappen, Departement Bio-ingenieurswetenschappen
Otitis media with effusion (OME) is a common childhood disease characterized by accumulation of fluid in the middle ear without symptoms of an acute infection. Chronic OME, lasting longer than three months, is often treated by placing a drainage tube into the ear drum, and there is an urgent need to develop non-invasive treatment and prevention methods. All bacteria traditionally associated with middle ear diseases are commensals also found in the upper respiratory tract (URT) of healthy individuals. Interaction with the host immune system and other bacteria present in the same niche determine their ability to expand into neighbouring anatomic locations and to express their virulence. Long-term perturbation of the microbiota has been associated with several chronic inflammatory diseases and is also hypothesized to underlie chronic OME. Preventing such perturbation or restoring a perturbed microbiota through addition of beneficial bacteria could therefore be a valuable method for OME prevention, reducing the need for surgical intervention.
This project aimed to identify bacteria associated with or protective against chronic OME. We first compared the microbiome of several URT and ear niches of 70 chronic OME patients and 63 healthy controls by sequencing the diverse V4 region of the bacterial 16S rRNA gene. This allowed us to identify bacterial taxa over-represented in healthy individuals or dominant in OME middle ear effusion. Next, we isolated health-associated bacteria and predicted their beneficial effect, ability to survive in the human URT and their safety through in vitro experimentation and genome analysis.
OME middle ear effusion frequently harboured one of several dominant (>50% relative abundance) taxa likely responsible for OME, which were traced to the URT and the ear canal. In contrast, most healthy middle ear rinses could not be sequenced, indicating very low biomass in or even sterility of this niche. Therefore, potentially health-associated bacteria were identified by comparing the nasopharynx microbiome between OME patients and healthy controls. Salivarius group streptococci and Acinetobacter lwoffi were significantly more abundant in the nasopharynx of healthy children compared to OME patients, but only the Streptococcus taxon was present in ≥50% of children and could be isolated. Seven Streptococcus salivarius isolates were characterized in detail and five were free of known virulence and transferable antibiotic resistance genes, inhibited all tested pathogens and adhered well to respiratory epithelial cells. This makes them promising candidates for further testing and development as potential probiotics or microbiome therapeutics to prevent or treat OME.